The grant is designed to cover new secondary metabolites from higher plants which have novel chemical structures and which have potential for clinical use as antibiotics in the treatment of infections caused by microorganisms against which current fermentation-derived antibiotics are unsatisfactory in some significant way. Central to this effort is the use of rational modern testing methods and the proven presence amongst higher plant extracts of structurally and therapeutically novel agents. Once confirmed to be active, the most potent plant extracts are fractionated guided by bioassay techniques in order to isolate the active constituents in pure form. These products are then evaluated for their antimicrobial spectrum and comparative potency in vitro in comparison with established antibiotics. In vivo evaluation in infected mice is carried out on the most potent agents. The new agents uncovered are often present in small amount so synthesis often has to be explored in order to confirm the structures, prepare enough for significant evaluation and to prepare analogues to explore the relationship between structure and activity. The latter is necessary because there are usually no precedent structures in the antibiotic literature to guide us and because of our desire to improve the medicinal potential of substances whose intrinsic activity is too weak for clinical use by themselves. The diseases under attack by these methods include tuberculosis, infections due to Gram-negative bacteria, venereal diseases, infections by organisms resistant to known antibiotics and fungal diseases.